The present invention relates to novel pyrimidine-2,4,6-trione compounds which are effective in absorbing ultra violet radiation and to light screening compositions containing such pyrimidine-2,4,6-trione compounds.
Light screening compositions containing pyrimidine-2,4,6-trione compounds are described in WO 98/14423. This publication refers, inter alia, to compounds of the general formula: 
wherein
R is alkyl, cyclic alkyl, aralkyl or aryl; and
Ra and Rb are each independently hydrogen, alkyl, cyclic alkyl, aralkyl and aryl.
This publication discloses that such compounds have an excellent ultraviolet absorbing ability. These compounds, however, are sensitive to hydrolytic decomposition.
It has now been found that compounds of the above formula in which the xe2x80x94COOR group is replaced by an ether group xe2x80x94OR or an ester group xe2x80x94OCOR surprisingly exhibit superior chemical stability.
Thus, one embodiment of the invention are compounds of the general formula I 
wherein
R1 and R2 are each independently C2-C18 alkyl, C5-C7 cycloalkyl or C2-C18 alkyl in which at least one methylene group is replaced by oxygen;
R3 is hydrogen, C1-C18 alkyl, C2-C18 alkyl in which at least one methylene group is replaced by oxygen, C1-C18 alkyl carbonyl, C3-C18 alkenyl, C3-C18 alkynyl, or a group YS;
R4 is hydrogen, C1-C8 alkyl or a group OR3;
Y is a linker group; and
S is a silane-, an oligosiloxane- or a polysiloxane moiety.
Another embodiment of the invention are light screening compositions containing a compound of formula I.
A further embodiment of the invention is a method for protecting a surface of a substrate from ultraviolet light. This method includes applying to a surface of a substrate a UV-blocking amount of a light screening composition containing a cosmetic base and a compound of formula I.
In the compounds of formula I, R1 and R2 may be the same or different. Preferably, R1 and R2 have the same meaning and are ethyl, propyl, isopropyl, n-butyl, sec. butyl, tert. butyl, 2-ethyl hexyl or cyclohexyl. Particularly preferred is isopropyl.
The residue OR3 is preferably in the para position. R3 preferably is C2-C8 alkyl or a group YS, more preferably 2-ethyl hexyl or a group YS.
The residue R4 preferably is hydrogen or hydroxy.
In the present invention, the term xe2x80x9cC1-C18 alkylxe2x80x9d means straight chain or branched saturated hydrocarbon residues with 1 to 18 carbon atoms such as methyl, ethyl, propyl, isopropyl, thexyl, (1,1,2 trimethyl-1-propyl), n-butyl, sec. butyl, tert. butyl, pentyl, neopentyl, hexyl, 2-ethyl-hexyl, octyl and the like.
The term xe2x80x9cC5-C7 cycloalkylxe2x80x9d means saturated hydrocarbon rings with 5 to 7 carbon atoms, i.e. cyclopentyl, cyclohexyl, and cycloheptyl.
The term xe2x80x9cC2-C18 alkyl in which at least one methylene group is replaced by oxygenxe2x80x9d means straight chain or branched saturated hydrocarbon residues with up to 17 carbon atoms which are bound via a carbon atom and have at least one group such as xe2x80x94(CH2xe2x80x94O)xe2x80x94, xe2x80x94(CH2xe2x80x94CH2xe2x80x94O)xe2x80x94, xe2x80x94(CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94O)xe2x80x94, xe2x80x94(CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94O)xe2x80x94, and the like.
In the term xe2x80x9cC1-C18 alkyl carbonyl,xe2x80x9d the alkyl residue is as defined above.
The term xe2x80x9cC3-C18 alkenylxe2x80x9d means straight chain or branched unsaturated hydrocarbon residues with 3 to 18 carbon atoms containing at least one double bond such as propen-2-yl, propen-3-yl, buten-3-yl, buten-4-yl, penten-4-yl, penten-5-yl, and the like.
The term xe2x80x9cC3-C18 alkynylxe2x80x9d means straight chain or branched unsaturated hydrocarbon residues with 3 to 18 carbon atoms containing at least one triple bond. A preferred alkynyl residue is propargyl.
As used herein, the phrase xe2x80x9clinker groupxe2x80x9d means a C3-C12 divalent alkylene or alkylene chain which links the UV absorbing chromophoric residue to the silane, oligosiloxane or polysiloxane moiety.
The term xe2x80x9cC3-C12 divalent alkylene chainxe2x80x9d means straight chain or branched saturated hydrocarbon residues such as 3-propylene, 2-propylene, 2-methyl-3-propylene, 3-butylene, 4-butylene, 4-pentylene, 5-pentylene, 6-hexylene, and the like.
The term xe2x80x9cC3-C12 divalent alkenylene chainxe2x80x9d means unsaturated hydrocarbon residues containing at least one double bond, such as for example, 2-propen-2-ylene, 2-propen-3-ylene, 3-buten-3-ylene 3-buten-4-ylene, 4-penten-4-ylene, 4-penten-5-ylene, (3-methyl)-penta-2,4-dien-4 or 5-ylene, 11-dodecen-11-ylene, and the like.
The divalent alkylene or alkenylene chains may be interrupted by one or several oxygen atoms. Examples of oxygen interrupted linker groups are e.g. 2-ethyloxy-eth-2-ylene, 4-butyloxy-eth-2-ylene or 3,6-dioxa-8-octylen. The linker groups of the present invention include 3-propylene, 4-butylene, 2-propen-2-ylene, 2-propen-3-ylene or 3-buten-4-ylene, preferably 2-propen-2-ylene or 2-propen-3-ylene.
The term xe2x80x9csilanexe2x80x9d means a group xe2x80x94SiR5R6R7, wherein R5, R6 and R7 are each independently C1-C6 alkyl or phenyl. Preferred silane groups are e.g. trimethylsilane, triethylsilane, tripropylsilane, triisopropylsilane, dimethyl tert.butylsilane, dimethyl thexylsilane, triphenylsilane, dimethylphenylsilane and the like.
As used herein, the term xe2x80x9coligosiloxanexe2x80x9d means groups of the general formula xe2x80x94SiR8m(OSiR8xe2x80x23)n where m=0, 1 or 2; n=1, 2 or 3, m+n=3, and wherein R8xe2x80x2 are each independently C1-C6 alkyl or phenyl. Preferably R8 and R8xe2x80x2 have the same meaning. Preferably, the oligosiloxane is xe2x80x94SiMe(OSiMe3)2, wherein Me is methyl.
As used herein, the term xe2x80x9coligosiloxanexe2x80x9d also includes groups of formulae IIa or IIb: 
wherein R9 is C1-C6 alkyl or phenyl and r is an integer from 1 to 9, preferably 1 to 3. The residue R9 is preferably C1-C4 alkyl, such as for example, methyl.
As used herein, the term xe2x80x9cpolysiloxanexe2x80x9d means groups of formulae IIIa or IIIb: 
wherein
R10 is C1-C6 alkyl or phenyl;
s is an integer from 4 to 250;
t is an integer from 5 to 250; and
q is an integer from 1 to 30.
Preferably, xe2x80x9csxe2x80x9d is an integer from 4 to 150. Preferably, xe2x80x9cqxe2x80x9d is an integer from 2 to 10, such as for example, it has statistical mean value of about 4. Preferably, xe2x80x9ctxe2x80x9d is an integer from 5 to 150, such as for example, it has statistical mean value of about 60. The residue R10 is preferably C1-C4 alkyl, such as for example, methyl.
The compounds of the general formula I may be prepared by methods known per se. For example, in compounds of the general formula I, wherein R3 is C1-C18 alkyl, C2-C18 alkyl in which at least one methylene group is replaced by oxygen, C3-C18 alkenyl or C3-C18 alkynyl, and R4 is hydrogen or C1-C8 alkyl, the process starts by alkylation of a nitrophenol of the formula IVa: 
wherein R4xe2x80x2 is hydrogen or C1-C8 alkyl; with an alkyl halide to provide a nitro phenolic ether IVb as set forth below: 
The alkyl halide has the formula R3xe2x80x2 Hal, wherein
R3xe2x80x2 is C1-C18 alkyl, C2-C18 alkyl in which at least one methylene group is replaced by oxygen, C3-C18 alkenyl or C3-C18 alkynyl; and
Hal is chloro, bromo or iodo, preferably, chloro or bromo.
The starting nitrophenol is commercially available or may be readily prepared by known methods.
The reaction is run in a suitable reaction solvent. The choice of the solvent is not critical. Suitable solvents include toluene, pyridine or polar aprotic solvents, such as e.g., 1-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, dioxane, tetrahydrofuran, acetonitrile, and the like. The reaction mixture includes an acid acceptor, such as a mild base, for example, sodium or potassium carbonate, which can absorb the acid-by-product of the alkylation. The reactants usually are present in about equal molar amounts and the reaction is run at an elevated temperature, e.g. at about 80xc2x0 C.-150xc2x0 C., preferably at about 100xc2x0 C.
The nitro phenolic ether (IVb) obtained is then reduced either by conventional methods using reduction with tin or zinc and hydrochloric acid or by catalytic hydrogenation to afford the corresponding amino group to provide the p-amino phenolic ether of the formula IVc. The catalytic hydrogenation is employed, using conventional catalysts such as Raney-nickel, palladium or platinum. The catalytic hydrogenation is carried out at temperatures in the range of 0xc2x0 C. to about 100xc2x0 C., preferably at about 20xc2x0 C. to about 60xc2x0 C., such as for example, at about 40xc2x0 C. and under atmospheric pressure to about 100 bar, preferably at about 20 bar to about 60 bar, such as for example, at about 40 bar.
Nitro phenolic ether compounds wherein R3, is C3-C18 alkenyl or C3-C18 alkynyl are preferably reduced using tin and hydrochloric acid.
Compounds of the general formula I, wherein R3 is C1-C18 alkyl, C2-C18 alkyl in which at least one methylene group is replaced by oxygen, C3-C18 alkenyl or C3-C18 alkynyl and R4 is a group OR3xe2x80x2 may also be prepared. 
The group R3xe2x80x2 is as defined above.
Compounds of the general formula I, wherein R3 is C1-C18 alkyl, C2-C18 alkyl in which at least one methylene group is replaced by oxygen, C3-C18 alkenyl or C3-C18 alkynyl and R4 is hydroxy (OR3 with R3=H) may be prepared using a conventional protective group for the hydroxy group such as e.g. ether-type protective groups or acetal-type protective groups.
Compounds of the general formula I, wherein R3 is hydrogen and R4 is hydrogen or C1-C8 alkyl may be prepared by reducing the corresponding nitro phenol IVa-b using conventional methods. 
R4xe2x80x2 is as defined above.
The pyrimidine-2,4,6-trione residue of the general formula V: 
wherein R1 and R2 are as defined above may be prepared as set forth below be adding malonic acid in an equimolar quantity to a carbodiimide of the general formula R1xe2x80x94N-xe2x95x90Cxe2x95x90Nxe2x80x94R2,
wherein R1 and R2 are as defined above. The reaction is run in a suitable reaction solvent. The choice of the solvent is not critical. Preferred solvents are polar aprotic solvents as listed above. 
Other methods to prepare the pyrimidine-2,4,6-trione residue of the general formula V, starting from e.g. malonic ester and dialkyl urea are described in WO 95/00112.
Finally, residue V is linked with residue IV by condensation in the presence of trialkyl orthoformate, preferably triethyl orthoformate (CH(OC2H5)3) to form compound VII: 
wherein R1, R2 and R3xe2x80x2 are as defined above, and R4xe2x80x3 is hydrogen, C1-C8 alkyl or OR3xe2x80x2.
The condensation is carried out in a solvent at reflux temperatures for several hours. The choice of the solvent is not critical. Preferred solvents are polar aprotic solvents as listed above.
For preparing a compound of the general formula I, it is also possible to first prepare an intermediate of the general formula VIla: 
wherein R1, R2 and R4xe2x80x3 are as defined above by reacting a amino phenol with a pyrimidine 2,4,6-trione compound in the presence of trialkyl orthoformate, preferably triethyl orthoformate (CH(OC2H5)3) and then alkylating the resulting intermediate of the formula VIIa.
Compounds of the general formula I, wherein R3 is C1-C18 alkyl carbonyl and R4 is hydrogen or C1-C8 alkyl may be prepared by acylating the compound of formula VIIa using known esterification reactions.
Compounds of formula I containing a silane-, an oligosiloxane- or a polvsiloxane moiety are prepared by hydrosilation. The following reaction scheme shows an example of how to prepare a compound of formula I wherein R3 is a group YS, S is a an oligosiloxane of the formula xe2x80x94SiR8m(OSIR8xe2x80x23)n, m=0 1 or 2; n=1, 2 or 3, and m+n=3, wherein R8xe2x80x2 are each independently C1-C6 alkyl or phenyl and R4xe2x80x2 is as defined above, namely hydrogen or C1-C8 alkyl. 
The hydrosilation reaction between the SiH group and the alkynyl group (step D) is carried out in the presence of a transition metal catalyst, e.g. platinum on charcoal or a platinum complex catalyst, such as e.g. divinyl-tetramethyl disiloxane platinum complex. The reaction is run in a suitable reaction solvent, such as e.g. in toluene. The reactants usually are present in about equal molar amounts and the reaction is run at a somewhat elevated temperature, e.g. at about 60xc2x0 C.-150xc2x0 C., preferably at about 40xc2x0 C.-100xc2x0 C., such as for example, at about 80xc2x0 C.
Compounds of formula I containing an oligosiloxane moiety of formula IIa or IIb or a polysiloxane moiety of formula IIIa or IIIb are prepared accordingly. The reaction partner is the corresponding SiH containing oligosiloxane or polysiloxane moiety.
The compounds of formula I have adsorption maxima in the range of 320 nm to 400 nm, the so called UV-A radiation.
The preparation of novel light screening agents, especially of preparations for skin protection and, respectively, sunscreen preparations for everyday cosmetics, includes incorporating a compound of formula I in a cosmetic base which is conventional for light screening agents. Where convenient, other conventional UV-A, and/or UV-B filters may also be combined in the light screening composition during this incorporation. The combination of UV filters may show a synergistic effect. Preparation of the light screening agents is well known to the skilled artisan in this field. The amount of compounds of formula I and other known UV-filters in the light screening compositions of the present invention is not critical. Suitable amounts are about 0.5 to about 12%.
Suitable UV-B filters for use in the present invention are substances having absorption maxima between about 290 and 320 nm, such as for example the following organic compounds:
Acrylates, such as 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene, PARSOL 340), ethyl 2-cyano-3,3-diphenylacrylate, and the like;
Camphor derivatives, such as 4-methyl benzylidene camphor (PARSOL 5000), 3-benzylidene camphor, camphor benzalkonium methosulfate, polyacrylamidomethyl benzylidene camphor, sulfo benzylidene camphor, sulphomethyl benzylidene camphor, therephthalidene dicamphor sulfonic acid, and the like;
Cinnamate derivatives, such as octyl methoxycinnamate (PARSOL MCX), ethoxyethyl methoxycinnamate, diethanolamine methoxycinnamate (PARSOL Hydro), isoamyl methoxycinnamate and the like, as well as cinnamic acid derivatives bond to siloxanes;
Organosiloxane compounds containing benzmalonate groups as recited in EP 0358584 B1, EP 0538431 B1 and EP 0709080 A1;
Pigments, such as microparticulated TiO2, and the like. As used herein, the term xe2x80x9cmicroparticulatedxe2x80x9d refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm. The TiO2 particles may also be coated by metal oxides, such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
Imidazole derivatives, such as e.g. 2-phenyl benzimidazole sulfonic acid and its salts (PARSOL HS). Salts of 2-phenyl benzimidazole sulfonic acid are e.g. alkali salts such as sodium- or potassium salts, ammonium salts, morpholine salts, salts of primary, sec. and tert. amines such as monoethanolamine salts, diethanolamine salts, and the like;
Salicylate derivatives, such as isopropylbenzyl salicylate, benzyl salicylate, butyl salicylate, octyl salicylate (NEO HELIOPAN OS), isooctyl salicylate or homomenthyl salicylate (homosalate, HELIOPAN), and the like;
Triazone derivatives, such as octyl triazone (UVINUL T-150), dioctyl butamido triazone (UVASORB HEB), and the like.
Suitable UV A filters for use in the present invention are substances having absorption maxima between about 320 and 400 nm, such as the following:
Dibenzoylmethane derivatives, such as 4-tert. butyl-4xe2x80x2-methoxydibenzol-methane (PARSOL 1789), dimethoxydibenzoylmethane, isopropyldibenzoylmethane and the like;
Benzotriazole derivatives, such as 2,2xe2x80x2-methylene-bis-(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3, -tetramethylbutyl)-phenol (TINOSORB M), and the like;
Pigments, such as microparticulated ZnO, and the like. The term xe2x80x9cmicroparticulatedxe2x80x9d refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm. The ZnO particles may also be coated by metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
Because dibenzoylmethane derivatives are photolabile, it is necessary to photostabilize these UV-A screening agents. Thus, the term xe2x80x9cconventional UV-A screening agentxe2x80x9d as used herein also refers to dibenzoylmethane derivatives, such as e.g. PARSOL 1789 stabilized by the following stabilizing agents:
3,3-Diphenylacrylate derivatives as described in EP 0 514 491 B1 and EP 0 780 119 A1;
Benzylidene camphor derivatives as described in Deflandre, et al., U.S. Pat. No. 5,605,680;
Organosiloxanes containing benzmalonate groups as described in EP 0358584 B1, EP 0538431 B1 and EP 0709080 A1.
As used herein, xe2x80x9ccosmetic basesxe2x80x9d for light screening compositions include any conventional preparation which corresponds to the desired cosmetic requirements, e.g. creams, lotions, emulsions, salves, gels, solutions, sprays, sticks, and milks. See, Sunscreens, Development, Evaluation and Regulatory Aspects, ed. N. Y. Lowe, N. A. Shaath, Marcel Dekker, Inc. New York and Basel, 1990.
Having regard to their good lipophilicity, the compounds of formula I may be incorporated well into oil and fat containing cosmetic preparations.
The following examples are provided to further illustrate the processes and compositions of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.